The goal of the project (initiated in July 1994) is to determine an optimal method for performing functional brain mapping studies with three-dimensional PET and oxygen-I5 water, a tracer used to measure regional cerebral blood flow (rCBF). Current tomographs, such as the GE Advance recently acquired by the NIH, permit 3D image acquisition and reconstruction, substantially increasing scanner sensitivity. However, image noise increases at the high count rates at which rCBF studies with bolus injections of 0-I5 water are typically performed. Thus, although the signal-to-noise ratio improves for low count rate studies, the improvement is much less at high count rates. As a result, one can perform CBF studies with smaller amounts of radioactivity, but it is not possible to inject the currently-used amounts to improve signal. There are several factors which affect the signal per mCi injected, including amount of radioactivity per injection, number of injections, and length and type of injection. Studies will he performed to find an optimal combination of these parameters for the GE Advance tomograph. Simulation, phantom, and human experiments will be performed. Simulations will be carried out to calculate the brain radioactivity that results from different 0-I5 water injection amounts and profiles, and varying scan lengths. In addition, data will be obtained on brain radioactivity per mCi of 0-15 water injected from scans previously performed with the Scanditronix PC2048-15B tomograph. Scan data will then be obtained on the GE Advance scanner using a brain phantom filled with decaying radioactivity for a range of count rates, and image noise will be determined per mCi in the scanner for specific scan lengths. The results of the phantom studies will he used to estimate the signal to noise properties resulting from the brain radioactivity levels for different scan protocols as predicted by the simulations. Based on these results, studies in humans will be performed with selected injection protocols while they perform a functional task that activates specific brain regions. The ability to detect activation foci with different protocols will be determined by analyzing the PET images with Statistical Parametric Mapping software. Ideally, a scan protocol will be determined to optimize detection of activation foci for a given total amount of radioactivity administered.